Identification of a novel subpopulation of Caspase-4 positive non-small cell lung Cancer patients

Michela Terlizzi, Chiara Colarusso, Ilaria De Rosa, Pasquale Somma, Carlo Curcio, Rita P. Aquino, Luigi Panico, Rosario Salvi, Federica Zito Marino, Gerardo Botti, Aldo Pinto, Rosalinda Sorrentino

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Therapy/prognosis of Non-Small Cell Lung Cancer (NSCLC) patients are strongly related to gene alteration/s or protein expression. However, more than 50% of NSCLC patients are negative to key drugable biomarkers. Methods: We used human samples of NSCLC and mouse models of lung adenocarcinoma. Results: We showed that caspase-4 was highly present in the tumor mass compared to non-cancerous human tissues. Interestingly, the orthologue murine caspase-11 promoted lung carcinogenesis in mice. Carcinogen-exposed caspase-11 knockout mice had lower tumor lesions than wild type mice, due to the relevance of caspase-11 in the structural lung cell as demonstrated by bone marrow transplantation and adoptive transfer experiments. Similarly to what observed in mice, caspase-4 was correlated to the stage of lung cancer in humans in that it induced cell proliferation in a K-Ras, c-MyC and IL-1α dependent manner. Caspase-4 positive adenocarcinoma (79.3%) and squamous carcinoma (88.2%) patients had lower median survival than patients who had lower levels of caspase-4. Moreover, PD-L1 expression and gene mutation (i.e. EGFR) were not correlated to caspase-4 expression. Instead, NSCLC patients who had K-Ras or c-MyC gene alteration were positively correlated to higher levels of caspase-4 and lower survival rate. Conclusions: We identified a subgroup of NSCLC patients as caspase-4 positive among which double and triple positive caspase-4, K-Ras and/or c-MyC patients which prognosis was poor. Because K-Ras and c-MyC are still undrugable, the identification of caspase-4 as a novel oncoprotein could introduce novelty in the clinical yet unmet needs for NSCLC patients.

Original languageEnglish
Article number242
JournalJournal of Experimental and Clinical Cancer Research
Volume39
Issue number1
DOIs
Publication statusPublished - Dec 2020

Keywords

  • Caspase-4
  • Cell proliferation
  • cMyc
  • K-Ras
  • Lung cancer
  • Oncoprotein
  • Survival rate
  • Tumor progression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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